Comparison of Shear Bond Strength and Microleakage between Activa™ Bioactive Restorative™ and Bulk-Fill Composites-An In Vitro Study.

Bioactive materials have emerged as a promising alternative to conventional restorative materials as part of more conservative dentistry. The aim of this study was to evaluate and compare the shear bond strength (SBS) and microleakage of a new bioactive restorative material, two bulk-fill restorative composites, and a conventional composite at 24 h, 4 weeks, and 8 weeks. Three hundred and sixty molars and premolars were divided into four groups: ACTIVA™ BioACTIVE Restorative™, Filtek™ Bulk-Fill Restorative Composite, Tetric® N-Ceram Bulk-Fill Composite, and G-aenial® Composite. The normality of the data was determined with the Kolmogorov-Smirnov test, then the two-way ANOVA and Fisher's test were used for analyzing SBS data, and the Kruskal-Wallis and DSCF tests were conducted to analyze the microleakage. In the SBS test, there were no statistically significant differences between materials (p = 0.587), and the relation between material and time (p = 0.467), time points showed statistically significant differences (p = 0.016). As for the microleakage, statistically significant differences were found for all three time periods (p < 0.05), showing the conventional composite to have the lowest microleakage, followed by the bioactive material, and lastly the two bulk-fill composites. In conclusion, the new bioactive material has similar evaluated properties to bulk-fill composites (bond strength) and conventional composites (bond strength and microleakage) and can be used as an alternative restorative material.

Epidemiology of clinically significant forms of alpha- and beta-thalassemia: A global map of evidence and gaps.

This systematic literature review assessed the global prevalence and birth prevalence of clinically significant forms of alpha- and beta-thalassemia. Embase, MEDLINE, and the Cochrane Library were searched for observational studies published January 1, 2000, to September 21, 2021. Of 2093 unique records identified, 69 studies reported across 70 publications met eligibility criteria, including 6 records identified from bibliography searches. Thalassemia prevalence estimates varied across countries and even within countries. Across 23 population-based studies reporting clinically significant alpha-thalassemia (e.g., hemoglobin H disease and hemoglobin Bart's hydrops fetalis) and/or beta-thalassemia (beta-thalassemia intermedia, major, and/or hemoglobin E/beta-thalassemia), prevalence estimates per 100 000 people ranged from 0.2 in Spain (over 2014-2017) to 27.2 in Greece (2010-2015) for combined beta- plus alpha-thalassemia; from 0.03 in Spain (2014-2017) to 4.5 in Malaysia (2007-2018) for alpha-thalassemia; and from 0.2 in Spain (2014-2017) to 35.7 to 49.6 in Iraq (2003-2018) for beta-thalassemia. Overall, the estimated prevalence of thalassemia followed the predicted pattern of being higher in the Middle East, Asia, and Mediterranean than in Europe or North America. However, population-based prevalence estimates were not found for many countries, and there was heterogeneity in case definitions, diagnostic methodology, type of thalassemia reported, and details on transfusion requirements. Limited population-based birth prevalence data were found. Twenty-seven studies reported thalassemia prevalence from non-population-based samples. Results from such studies likely do not have countrywide generalizability as they tended to be from highly specific groups. To fully understand the global prevalence of thalassemia, up-to-date, population-based epidemiological data are needed for many countries.

State of the Art of Different Zirconia Materials and Their Indications According to Evidence-Based Clinical Performance: A Narrative Review.

The aim of this study was to perform a narrative review to identify the modifications applied to the chemical structure of third- and fourth-generation zirconia ceramics and to determine the influence of these changes on the mechanical and optical properties. A bibliographical search using relevant keywords was conducted in the PubMed® and EBSCO databases. The abstracts and full texts of the resulting articles were reviewed for final inclusion. Fifty-four articles were included in this review. The analyzed topics were: (1) the composition of first- and second-generation zirconia materials (Y-TZP), (2) the behavior of the studied generations in relation to mechanical and optical properties, and (3) the modifications that were carried out on third-generation (5Y-TZP) and fourth-generation (4Y-TZP) zirconia materials. However, studies focusing on these specific characteristics in third- and fourth-generation zirconia materials are scarce. The review shows that there is a lack of sufficient knowledge about the chemical modifications of zirconia in the new generations.

Cardiopulmonary Imaging Utilization and Findings among Hospitalized COVID-19 Patients in Latin America: (From "RIMAC: Registry IMAging Cardiopulmonary among Hospitalized COVID-19 Patients in LATAM").

Objectives: Describe the use and findings of cardiopulmonary imaging-chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS), and/or cardiac magnetic resonance imaging (cMRI)-in COVID-19 hospitalizations in Latin America (LATAM). Background: There is a lack of information on the images used and their findings during the SARS-CoV-2 pandemic in LATAM. Methods: Multicenter, prospective, observational study of COVID-19 inpatients, conducted from March to December 2020, from 12 high-complexity centers, in nine LATAM countries. Adults (>18 years) with at least one imaging modality performed, followed from admission until discharge and/or in-hospital death, were included. Results: We studied 1,435 hospitalized patients (64% males) with a median age of 58 years classified into three regions: Mexico (Mx), 262; Central America and Caribbean (CAC), 428; and South America (SAm), 745. More frequent comorbidities were overweight/obesity, hypertension, and diabetes. During hospitalization, 58% were admitted to the ICU. The in-hospital mortality was 28%, and it was highest in Mx (37%).The most frequent images performed were cCT (61%), mostly in Mx and SAm, and cX-ray (46%), significant in CAC. The cEcho was carried out in 18%, similarly among regions, and LUS was carried out in 7%, with a higher frequently in Mx. Abnormal findings on the cX-ray were peripheral or basal infiltrates, and in cCT abnormal findings were the ground glass infiltrates, more commonly in Mx. In LUS, interstitial syndrome was the most abnormal finding, predominantly in Mx and CAC.Renal failure was the most prevalent complication (20%), predominant in Mx and SAm. Heart failure developed in 13%, predominant in Mx and CAC. Lung thromboembolism was higher in Mx while myocardial infarction was in CAC.Logistic regression showed associations of abnormal imaging findings and their severity, with comorbidities, complications, and evolution. Conclusions: The use and findings of cardiopulmonary imaging in LATAM varied between regions and had a great impact on diagnosis and prognosis.

Hepatitis autoinmune en pediatría, una revisión del Grupo de Trabajo de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (LASPGHAN) / Autoimmune hepatitis in pediatrics, a review by the Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology, and Nutrition

La hepatitis autoinmunitaria es una enfermedad inflamatoria crónica del hígado caracterizada por una interacción compleja entre factores genéticos, respuesta inmunitaria a antígenos presentes en los hepatocitos y alteraciones de la regulación inmunitaria. Presenta una distribución global, con predominio en individuos de sexo femenino. Se clasifica en dos grupos, según el tipo de autoanticuerpos séricos detectados. La forma de presentación más frecuente es la hepatitis aguda (40 %), con síntomas inespecíficos, elevación de aminotransferasas e hipergammaglobulinemia. El tratamiento estándar consiste en la administración de fármacos inmunosupresores. Es una patología compleja, a veces difícil de diagnosticar. Si no se trata de manera adecuada, la mortalidad puede alcanzar el 75 % a los 5 años de evolución.

Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by a complex interaction among genetic factors, immune response to antigens present in hepatocytes, and immune regulation alterations. Its distribution is global and there is a female predominance. AIH is divided into 2 groups, depending on the type of serum autoantibodies detected. The most common presentation is acute hepatitis (40%), with nonspecific symptoms, high aminotransferase levels, and hypergammaglobulinemia. Standard treatment consists of the administration of immunosuppressive drugs. It is a complex condition, often difficult to diagnose. If not managed adequately, the 5-year mortality rate may reach 75%.

Autoimmune hepatitis in pediatrics, a review by the Working Group of the Latin American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. / Hepatitis autoinmune en pediatría, una revisión del Grupo de Trabajo de la Sociedad Latinoamericana de Gastroenterología, Hepatología y Nutrición Pediátrica (LASPGHAN).

Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by a complex interaction among genetic factors, immune response to antigens present in hepatocytes, and immune regulation alterations. Its distribution is global and there is a female predominance. AIH is divided into 2 groups, depending on the type of serum autoantibodies detected. The most common presentation is acute hepatitis (40%), with non-specific symptoms, high aminotransferase levels, and hypergammaglobulinemia. Standard treatment consists of the administration of immunosuppressive drugs. It is a complex condition, often difficult to diagnose. If not managed adequately, the 5-year mortality rate may reach 75%.

La hepatitis autoinmunitaria es una enfermedad inflamatoria crónica del hígado caracterizada por una interacción compleja entre factores genéticos, respuesta inmunitaria a antígenos presentes en los hepatocitos y alteraciones de la regulación inmunitaria. Presenta una distribución global, con predominio en individuos de sexo femenino. Se clasifica en dos grupos, según el tipo de autoanticuerpos séricos detectados. La forma de presentación más frecuente es la hepatitis aguda (40 %), con síntomas inespecíficos, elevación de aminotransferasas e hipergammaglobulinemia. El tratamiento estándar consiste en la administración de fármacos inmunosupresores. Es una patología compleja, a veces difícil de diagnosticar. Si no se trata de manera adecuada, la mortalidad puede alcanzar el 75 % a los 5 años de evolución.

Fracture Resistance in Non-Vital Teeth: Absence of Interproximal Ferrule and Influence of Preparation Depth in CAD/CAM Endocrown Overlays-An In Vitro Study.

There is ample evidence to support the use of endocrowns to restore endodontic teeth. However, the influence of the position of the interproximal margins on fracture strength has not yet been studied. The aim was to determine the relationship between the apicocoronal position of the interproximal restorative margins and fracture resistance in nonvital teeth restored with CAD/CAM endocrown overlays. Forty extracted human maxillary premolars were prepared for endocrown overlay restorations without ferrule on the interproximal aspects and classified according to the position of the interproximal restoration margins in relation to the alveolar crest: 2 mm (group A), 1 mm (group B), 0.5 mm (group C), and 0 mm (group D). Fracture strength was measured using a universal testing machine applying a compressive force to the longitudinal tooth axis. Group A had a mean fracture resistance of 859.61 (±267.951) N, group B 1053.9 (±333.985) N, group C 1124.6 (±291.172) N, and group D 780.67 (±183.269) N, with statistical differences between groups. Group C had the highest values for fracture strength compared to the other groups (p < 0.05). The location of the interproximal margins appears to influence the fracture resistance of CAD/CAM endocrown overlays. A distance of 0.5 mm between the interproximal margin and the alveolar crest was associated with increased fracture resistance.

Analysis of moral reasoning in dentistry students through case-based learning (CBL).

PURPOSE: The aim of this study was to develop a tool to analyze the ethical dimensions during dental students' decision making, by using case-based learning (CBL). METHODS: Five clinical scenarios involving ethical aspects addressing different moral dilemmas were selected. The cases were then administered to students during a course on ethics, and the students responded using a narrative technique. To analyze the responses, a criterion inspired by Kohlberg's theory of moral development was used. Subsequently, the data were analyzed statistically, and possible associations between the answers and other variables, such as the student's gender and theoretical knowledge of ethics, were evaluated. RESULTS: A total of 260 students participated (182 women and 78 men), and 1300 narratives were analyzed. The reliability of the construct, as tested by the Cronbach's alpha and the homogeneity index, was acceptable (0.7). The validity of the construct was also assessed, suggesting a component analysis. The descriptive analysis suggests a certain tendency to solve moral problems by referring to established norms and laws. Furthermore, the correlation anaylysis suggests the interrelation between dimensions linked to patient integrity and respect for the truth, even though this conclusion is not reflected in the component analysis, which only detects a generic component of moral sensitivity. No significant differences by gender were found in the narratives, nor a strong correlation of the responses with theoretical knowledge on ethics. CONCLUSION: CBL through the narrative method on ethical dilemmas is an effective tool for assessing dental students' moral competencies and their possible interactions with other variables.

Peer Mentoring as a Tool for Developing Soft Skills in Clinical Practice: A 3-Year Study.

Education currently focuses on improving academic knowledge and clinical skills, but it is also important for students to develop personal and interpersonal skills from the start of their clinical practice. The aim was to evaluate the effect of peer mentoring in third-year students and to gauge the evolution of non-technical skills (NTS) acquisition up to the fifth year. The study groups were selected between September 2015 and May 2018, based on the NTS training they had or had not received: (1) fifth-year students with no training (G1); (2) third-year students mentored in NTS (G2a); and (3) a small group of fifth-year students who became mentors (G2b). A total of 276 students who took part in this study were assessed using a 114-item self-evaluation questionnaire. Data were collected from seven surveys conducted between September 2015 and May 2018, and statistical analysis was performed using one-way ANOVA and Fisher's post-hoc test. G2a improved their non-technical skill acquisition over three years of clinical training up to their fifth year. This group and G2b showed statistically significant differences compared to non-mentored students (G1). Peer mentoring at the beginning of clinical practice is a valid option for training students in non-technical skills.

Fracture Resistance of Two Different Composite Resin CAD/CAM Crowns Bonded to Titanium Abutments.

PURPOSE: To determine the influence of thermal and mechanical cycling on fracture load and fracture pattern of resin nanoceramic crowns and polymer-infiltrated ceramic-network (PICN) crowns, both fabricated with CAD/CAM technology. MATERIALS AND METHODS: A total of 90 premolar crowns bonded to titanium abutments were divided into three groups of 30 crowns each: 30 resin nanoceramic crowns (LU); 30 PICN crowns (VE); and 30 metal-ceramic crowns (MC). The 30 specimens of each group were further divided into three subgroups of 10 each that underwent (1) no treatment, (2) thermocycling (2,000 cycles, 5°C to 55°C), and (3) thermocycling with subsequent mechanical cycling (120,000 cycles, 80 N, 2 Hz). The specimens were loaded to failure, and two-way ANOVA and chi-square test were used to determine differences in fracture resistance and pattern. RESULTS: Mechanical and thermal cycling significantly influenced the critical load to failure of the three materials; however, no significant differences were observed between the thermocycled materials and the materials that were thermocycled with subsequent mechanical cycling. The MC specimens experienced significantly higher fracture loads than those of the LU and VE specimens, which showed no differences from each other in fracture resistance. The fracture patterns showed chipping in MC crowns and partial or complete fracture in LU and VE crowns. The fracture pattern depended on the material and was unrelated to the type of treatment it underwent. CONCLUSION: All crowns showed adequate resistance to normal masticatory forces in the premolar area. The cyclic fatigue load negatively influenced all three materials.

Conscious sedation in Spanish dental schools: Current situation.

The current Spanish curricula for degrees in dentistry include conscious sedation (CS) as a basic training competency. However, is the CS training delivered by Spanish dental schools a consensus-based educational framework enabling students to use this anesthetic technique after graduation? To answer this research question, a study was designed aiming to identify the strategies used to teach this competency in Spanish dental schools and the characteristics of teaching. The authors reviewed legislation concerning officially established requirements for a degree in dentistry as well as curricula currently taught in Spain. Our analysis identified clear discrepancies among the schools of dentistry studied. The only overlap was observed in reference to the level of proficiency imparted, which prevents Spanish dentistry students from using this anesthetic technique after graduation. Specific features of the normative framework and of the Spanish legislative system underlying the design of the present curricula of degrees in dentistry would explain the discrepancies in CS competencies taught at our schools of dentistry. Almost 10 years since its implementation and in light of the new demands of the complex society in which we live, Spanish universities must unify their educational criteria regarding CS training to ensure the appropriate qualification of our new dentists in this technique.

Six-month color change and water sorption of 9 new-generation flowable composites in 6 staining solutions.

Color match and water sorption are two factors that affect restorative materials. Discoloration is essential in the lifespan of restorations. The aim of this study was to evaluate color change and water sorption of nine flowable composites at multiple time points over 6 months. 60 samples of each composite were divided into two groups (Color Change and Water Sorption/Solubility). Each Color Change group was divided into six subgroups, which were immersed in distilled water (DW), coffee (CF), Coca-Cola (CC), red wine (RW), tea (TE) and orange juice (OJ). The color was measured at the baseline, 1, 2, 3 and 4 weeks, and 3 and 6 months and color change values (ΔE) were calculated. Each Water Sorption [WS]/Solubility [WL] group was tested according to ISO 4049:2009. The data were evaluated using two-way ANOVA, Fisher's post-hoc test and Pearson's correlation test. The composite with the lowest ΔE differed for each solution: Filtek™ Bulk Fill in DW (∆E = 0.73 (0.17-1.759)); Vertise Flow in CF (∆E = 14.75 (7.91-27.41)), in TE (∆E = 7.27 (2.81-24.81)) and OJ (∆E = 3.17 (0.87-9.92)); Tetric EvoFlow® in CC (∆E = 1.27 (0.45-4.02)); and Filtek™ Supreme XTE in RW (∆E = 8.88 (5.23-19.59)). RW caused the most discoloration (∆E = 23.62 (4.93-51.36)). Vertise Flow showed the highest water sorption (WS = 69.10 ± 7.19). The Pearson test showed statistically significant positive correlations between water sorption and solubility and between water sorption and ∆E; the positive solubility-∆E correlation was not statistically significant. The findings suggest that water sorption is one factor associated with the ability of composites to discolor; however, discoloration is a multifactorial problem.

Six-month color change and water sorption of 9 new-generation flowable composites in 6 staining solutions

Abstract Color match and water sorption are two factors that affect restorative materials. Discoloration is essential in the lifespan of restorations. The aim of this study was to evaluate color change and water sorption of nine flowable composites at multiple time points over 6 months. 60 samples of each composite were divided into two groups (Color Change and Water Sorption/Solubility). Each Color Change group was divided into six subgroups, which were immersed in distilled water (DW), coffee (CF), Coca-Cola (CC), red wine (RW), tea (TE) and orange juice (OJ). The color was measured at the baseline, 1, 2, 3 and 4 weeks, and 3 and 6 months and color change values (ΔE) were calculated. Each Water Sorption [WS]/Solubility [WL] group was tested according to ISO 4049:2009. The data were evaluated using two-way ANOVA, Fisher's post-hoc test and Pearson's correlation test. The composite with the lowest ΔE differed for each solution: Filtek™ Bulk Fill in DW (∆E = 0.73 (0.17-1.759)); Vertise Flow in CF (∆E = 14.75 (7.91-27.41)), in TE (∆E = 7.27 (2.81-24.81)) and OJ (∆E = 3.17 (0.87-9.92)); Tetric EvoFlow® in CC (∆E = 1.27 (0.45-4.02)); and Filtek™ Supreme XTE in RW (∆E = 8.88 (5.23-19.59)). RW caused the most discoloration (∆E = 23.62 (4.93-51.36)). Vertise Flow showed the highest water sorption (WS = 69.10 ± 7.19). The Pearson test showed statistically significant positive correlations between water sorption and solubility and between water sorption and ∆E; the positive solubility-∆E correlation was not statistically significant. The findings suggest that water sorption is one factor associated with the ability of composites to discolor; however, discoloration is a multifactorial problem.

Fruit and Vegetable Consumption and Changes in Anthropometric Variables in Adult Populations: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

BACKGROUND: Randomized controlled trials provide conflicting results on the effects of increased fruit and vegetable consumption on changes in body weight. We aimed to perform a systematic review and meta-analysis of prospective cohort studies on fruit and vegetable consumption in relation to changes in anthropometric measures. METHODS: PubMed and EMBASE were searched up to July 2015 for prospective studies reporting on habitual fruit and/or vegetable consumption in relation to changes in body weight or waist circumference or to risk of weight gain/overweight/obesity in adults. Random-effects meta-analysis was applied to pool results across studies. FINDINGS: Seventeen cohort studies (from 20 reports) including 563,277 participants met our inclusion criteria. Higher intake of fruits was inversely associated with weight change (decrease) (beta-coefficient per 100-g increment, -13.68 g/year; 95% CI, -22.97 to -4.40). No significant changes could be observed for combined fruit and vegetable consumption or vegetable consumption. Increased intake of fruits was inversely associated with changes (decrease) in waist circumference (beta: -0.04 cm/year; 95% CI, -0.05 to -0.02). Comparing the highest combined fruit & vegetable, fruit, and vegetable intake categories were associated with a 9%, 17%, and 17% reduced risk of adiposity (odds ratio [OR]: 0.91, 95% CI, 0.84 to 0.99), (OR: 0.83, 95% CI, 0.71 to 0.99), and (OR: 0.83, 95% CI, 0.70 to 0.99), respectively. CONCLUSION: This meta-analysis showed several inverse associations between fruit and vegetable intake and prospective improvements in anthropometric parameters, and risk of adiposity. The present meta-analysis seems to be limited by low study quality. Nevertheless, when combined with evolutionary nutrition and epidemiological modeling studies, these findings have public health relevance and support all initiatives to increase fruit and vegetable intake.

Reproducibility of Retinol Binding Protein 4 and Omentin-1 Measurements over a Four Months Period: A Reliability Study in a Cohort of 207 Apparently Healthy Participants.

The reliability of single time point measurements of the novel adipokines retinol-binding protein 4 and omentin-1 in the blood has not been evaluated in large samples yet. The present study aimed to assess the amount of biological variation of these two adipokines within individuals. The study sample comprised 207 participants (124 women and 83 men) from Potsdam (Germany) and surrounding areas, with an average age of 56.5 years (SD 4.2). Blood samples were collected from each participant twice, approximately four months apart. Using enzyme linked immunosorbent assays, the concentrations of retinol-binding protein 4 and omentin-1 were determined in EDTA plasma. As indicators of reliability, intraclass correlation coefficients (ICCs) were calculated from the repeated biomarker measurements. The ICCs for repeated retinol-binding protein 4 and omentin-1 measurements were 0.77 (95% CI 0.71, 0.82) and 0.83 (95% CI 0.78, 0.87), respectively, indicating for both adipokines excellent reliability. ICCs were stable across strata according to sex, age, BMI, and blood pressure. Thus, for epidemiological studies it seems reasonable to rely on concentrations of retinol-binding protein 4 and omentin-1 in samples from a single time point if repeated measurements are not available.

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials.

BACKGROUND: In the Western world, dietary supplements are commonly used to prevent chronic diseases, mainly cardiovascular disease and cancer. However, there is inconsistent evidence on which dietary supplements actually lower risk of chronic disease, and some may even increase risk. We aim to evaluate the comparative safety and/or effectiveness of dietary supplements for the prevention of mortality (all-cause, cardiovascular, and cancer) and cardiovascular and cancer incidence in primary prevention trials. METHODS/DESIGN: We will search PubMed, EMBASE, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials, clinical trials.gov, and the World Health Organization International Trial Registry Platform. Randomized controlled trials will be included if they meet the following criteria: (1) minimum intervention period of 12 months; (2) primary prevention of chronic disease (is concerned with preventing the onset of diseases and conditions); (3) minimum mean age ≥18 years (maximum mean age 70 years); (4) intervention(s) include vitamins (beta-carotene, vitamin A, B vitamins, Vitamin C, Vitamin D, Vitamin E, and multivitamin supplements); fatty acids (omega-3 fatty acids, omega-6 fatty acids, monounsaturated fat); minerals (magnesium, calcium, selenium, potassium, iron, zinc, copper, iodine; multiminerals); supplements containing combinations of both vitamins and minerals; protein (amino acids); fiber; prebiotics; probiotics; synbiotics; (5) supplements are orally administered as liquids, pills, capsules, tablets, drops, ampoules, or powder; (6) report results on all-cause mortality (primary outcome) and/or mortality from cardiovascular disease or cancer, cardiovascular and/or cancer incidence (secondary outcomes). Pooled effects across studies will be calculated using Bayesian random effects network meta-analysis. Sensitivity analysis will be performed for trials lasting ≥5 years, trials with low risk of bias, trials in elderly people (≥65 years), ethnicity, geographical region, and trials in men and women. The results of the corresponding fixed effects models will also be compared in sensitivity analyses. DISCUSSION: This is a presentation of the study protocol only. Results and conclusions are pending completion of this study. Our systematic review will be of great value to consumers of supplements, healthcare providers, and policy-makers, regarding the use of dietary supplements. PROSPERO: CRD42014014801 .

Joint effect of unlinked genotypes: application to type 2 diabetes in the EPIC-Potsdam case-cohort study.

Analyzing multiple single nucleotide polymorphisms (SNPs) is a promising approach to finding genetic effects beyond single-locus associations. We proposed the use of multilocus stepwise regression (MSR) to screen for allele combinations as a method to model joint effects, and compared the results with the often used genetic risk score (GRS), conventional stepwise selection, and the shrinkage method LASSO. In contrast to MSR, the GRS, conventional stepwise selection, and LASSO model each genotype by the risk allele doses. We reanalyzed 20 unlinked SNPs related to type 2 diabetes (T2D) in the EPIC-Potsdam case-cohort study (760 cases, 2193 noncases). No SNP-SNP interactions and no nonlinear effects were found. Two SNP combinations selected by MSR (Nagelkerke's R² = 0.050 and 0.048) included eight SNPs with mean allele combination frequency of 2%. GRS and stepwise selection selected nearly the same SNP combinations consisting of 12 and 13 SNPs (Nagelkerke's R² ranged from 0.020 to 0.029). LASSO showed similar results. The MSR method showed the best model fit measured by Nagelkerke's R² suggesting that further improvement may render this method a useful tool in genetic research. However, our comparison suggests that the GRS is a simple way to model genetic effects since it does not consider linkage, SNP-SNP interactions, and no non-linear effects.

Delirium, agitation, and symptom distress within the final seven days of life among cancer patients receiving hospice care.

OBJECTIVE: Knowledge of symptom prevalence and adequate assessment of such symptoms at the end of life is important in clinical practice. We determined the frequency and severity of symptom distress and delirium using the Edmonton Assessment Scale (ESAS) and the Memorial Delirium Assessment Scale (MDAS) and evaluated the clinical utility of the Nursing Delirium Screening Scale (Nu-DESC) as scored by a caregiver as a screening tool for delirium. METHOD: We conducted a secondary analysis of the data from a previous randomized controlled trial on parenteral hydration at the end of life of patients admitted to home hospice. Only patients that had assessments within the last week of life were included. We collected the ESAS, MDAS, Nu-DESC, and Richmond Agitation Sedation Scale (RASS) results. The sensitivity and specificity of the Nu-DESC were then calculated. RESULTS: Some 78 of 261 patients were included in our study, 62 (80%) of which had moderate-to-severe symptoms corresponding to an ESAS score >4. These symptoms include: 73 (94%) anorexia, 63 (81%) fatigue, 56 (73%) drowsiness, 58 (75%) decreased well-being, and 39 (51%) pain. Delirium was diagnosed in 34 (44%) of patients using the MDAS. The Nu-DESC was found to have a sensitivity of 35%, a specificity of 80%, a positive predictive value (PPV) of 58%, and an negative predictive value (NPV) of 61% when used by caregivers. SIGNIFICANCE OF RESULTS: Hospice patients at the end of life have a high rate of symptom distress and delirium. The Nu-DESC is not a reliable tool for screening delirium when scoring is conducted by a caregiver. Our study illustrates the need for routine use of assessment tools to improve care.

Characteristics and outcomes of advanced cancer patients who miss outpatient supportive care consult appointments.

BACKGROUND: Missed appointments (MA) are frequent, but there are no studies on the effects of the first MA at supportive care outpatient clinics on clinical outcomes. METHODS: We determined the frequency of MA among all patients referred to our clinic from January-December 2011 and recorded the clinical and demographic data and outcomes of 218 MA patients and 217 consecutive patients who kept their first appointments (KA). RESULTS: Of 1,352 advanced-cancer patients referred to our clinic, 218 (16 %) had an MA. The MA patients' median age was 57 years (interquartile range, 49-67). The mean time between referral and appointment was 7.4 days (range, 0-71) for KA patients vs. 9.1 days (range, 0-89) for MA patients (P = 0.006). Reasons for missing included admission to the hospital (17/218 [8 %]), death (4/218 [2 %]), appointments with primary oncologists (37/218 [18 %]), other appointments (19/218 [9 %]), visits to the emergency room (ER) (9/218 [9 %]), and unknown (111/218 [54 %]). MA patients visited the ER more at 2 weeks (16/214 [7 %] vs. 5/217 [2 %], P = 0.010) and 4 weeks (17/205 [8 %] vs. 8/217 [4 %], P = 0.060). Median-survival duration for MA patients was 177 days (range, 127-215) vs. 253 days (range, 192-347) for KA patients (P = 0.013). Multivariate analysis showed that MAs were associated with longer time between referral and scheduled appointment (odds ratio [OR], 1.026/day, P = 0.030), referral from targeted therapy services (OR, 2.177, P = 0.004), living in Texas/Louisiana regions (OR, 2.345, P = 0.002), having an advanced directive (OR, 0.154, P < 0.0001), and being referred for symptom control (OR, 0.024, P = 0.0003). CONCLUSION: MA patients with advanced cancer have worse survival and increased ER utilization than KA patients. Patients at higher risk for MA should undergo more aggressive follow-up. More research is needed.

Evaluación multidimensional de la astenia relacionada con el cáncer / Cancer related fatigue: a multidimensional evaluation

La astenia en el paciente con cáncer es definida como una sensación abrumadora y persistente de cansancio o agotamiento relacionado con el cáncer o el tratamiento de este, que disminuye o impide la capacidad para el trabajo mental o físico en el contexto de su actividad diaria y a pesar de un buen descanso. Es uno de los primeros síntomas que puede presentarse en el paciente con cáncer, afectando de manera importante a la calidad de vida. El objetivo de esta revisión es detallar las diferentes causas que influyen en la astenia y describir las escalas de medida que más frecuentemente se utilizan para estudiarla. La metodología empleada en esta revisión es narrativa. En esta revisión describimos cómo la astenia es un concepto multidimensional, ya que casi siempre está provocada o influenciada por múltiples causas. Esta multidimensionalidad interviene también en la comprensión de la fisiopatología. Por esta razón en esta revisión diferenciaremos entre astenia primaria y secundaria definiendo y detallando cada una de ellas. Por otro lado, también analizamos el tipo de escalas empleadas para medir la astenia diferenciando entren las que miden la astenia de forma primaria o las que la miden desde un punto de vista multidimensional

Fatigue in cancer patients is defined as an unusual, persistent, subjective sense of tiredness related to cancer or cancer treatment that interferes with usual functioning, despite good rest. Fatigue is one of the first symptoms that can appear in patients with cancer and quality of life is severely impacted by it. The main goal of this review is to describe the different causes that influence fatigue and the different ways to asses this symptom. The methodology we have used for this review is narrative. In this work we describe fatigue as a multidimensional concept that it is caused by multiple mechanisms. This multidimensionality is also involved in understanding the pathophysiologyFor that reason we are going to define fatigue as primary and secondary, and we are going to describe each of them. We are also going to analyse the type of scales used to measure fatigue; describing the differences between the ones that measure only fatigue and the ones that are used to asses fatigue from a multidimensional perspective